tbuckley/cabot-search huggingface dataset:
Global Trends in the Proportion of Macrolide-Resistant <i>Mycoplasma pneumoniae</i> Infections
Authors: Kyunghoon Kim, Sungsu Jung, Mina Kim, Suyeon Park, Hyeon-Jong Yang, Eun Lee
Journal: JAMA Network Open (2022)

<h3>Importance</h3> The proportion of macrolide-resistant<i>Mycoplasma pneumoniae</i>(MRMP) infections has changed, and it differs according to geographical region. <h3>Objective</h3> To analyze the global patterns, including the temporal trends, regional variations, and variant types, in the proportion of MRMP infections in this systematic review and meta-anaysis. <h3>Data Sources</h3> PubMed, Cochrane Library, and Embase databases were searched for observational studies from inception to September 10, 2021. <h3>Study Selection</h3> Observational studies reporting the proportion of MRMP infections were screened independently by 2 authors. The presence of MRMP infection was defined as any case of<i>M pneumoniae</i>infection positive for any variants associated with macrolide resistance identified using respiratory samples. <h3>Data Extraction and Synthesis</h3> Data were extracted independently and in duplicate by 2 reviewers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was used. Random-effects meta-analyses were used to estimate the proportion of MRMP infections. <h3>Main Outcomes and Measures</h3> The global patterns in the proportion of MRMP infections were estimated, and the temporal trends and variant types of MRMP infection with regional differences were investigated. <h3>Results</h3> This study included 153 studies from 150 articles (27 408 samples in 26 countries) in the meta-analysis. The global patterns in the proportion of MRMP infections showed an increasing trend with regional differences. The proportion of MRMP infections was highest in the Western Pacific regions (53.4%; 95% CI, 47.4%-60.3%), followed by the South East Asian region (9.8%; 95% CI, 0.8%-100%), the region of the Americas (8.4%; 95% CI, 6.1%-11.6%), and the European region (5.1%; 95% CI, 3.3%-8.0%). The most commonly identified variant of MRMP infection was A2063G (96.8%; 95% CI, 95.8%-97.7%), followed by A2064G (4.8%; 95% CI, 3.5%-6.7%). The proportion of MRMP infections was the highest in studies including only children (37.0%; 95% CI, 29.8%-46.1%), followed by those including only adults (15.9%; 95% CI, 6.4%-39.7%) and those including both children and adults (16.7%; 95% CI, 10.1%-27.6%). <h3>Conclusions and Relevance</h3> This study provides global trends in the proportion of MRMP infections and suggests that strategies to prevent the spread of MRMP infection and to treat MRMP infections are needed to decrease disease burden.
Dysregulation of Bile Acids, Lipids, and Nucleotides in Psoriatic Arthritis Revealed by Unbiased Profiling of Serum Metabolites
Authors: Ananta Paine, Paul S. Brookes, Soumyaroop Bhattacharya, Dongmei Li, Maria De La Luz Garcia‐Hernandez, Francisco Tausk, Christopher Ritchlin
Journal: Arthritis & Rheumatology (2022)

The transition from psoriasis to psoriatic arthritis (PsA) occurs in 20-30% of patients; however, the mechanisms underlying the emergence of musculoskeletal disease are not well understood. Metabolic disease is prevalent in psoriasis patients, but whether metabolic factors, other than obesity, increase arthritis risk in psoriasis patients is not known. This study was undertaken to investigate the link between metabolic changes and disease progression in psoriasis patients.
Dupilumab significantly improves skin barrier function in patients with moderate‐to‐severe atopic dermatitis
Authors: Evgeny Berdyshev, Elena Goleva, Robert Bissonnette, Irina Bronova, Anna Sofia Bronoff, Brittany N. Richers, Shannon Garcia, Marco Ramirez‐Gama, Patricia Taylor, Amy Praestgaard, Inoncent Agueusop, Pauline Jurvilliers, Mark Boguniewicz, Noah A. Levit, Ana B. Rossi, Annie Zhang, Donald Y. M. Leung
Journal: Allergy (2022)

Abstract Background Atopic dermatitis (AD) is characterized by abnormal skin lipids that are largely driven by hyperactivated type 2 immune responses. The antibody to the α‐subunit of interleukin (IL)‐4 receptor, dupilumab, was recently approved to treat AD and demonstrated strong efficacy. However, the role of dupilumab therapy in the regulation of skin barrier structure and function has not been fully explored. Methods We have evaluated the content of lipids and transepidermal water loss (TEWL) in lesional and non‐lesional skin of adults and adolescents with moderate‐to‐severe AD over the course of 16‐week treatment with dupilumab and compared those values with that of matched healthy volunteers. Results Dupilumab treatment provided a significant decrease in TEWL in AD lesions, lowering it almost to the levels seen in the skin of healthy subjects. Blocking IL‐4/IL‐13 signaling with dupilumab normalized lipid composition (decreased levels of ceramides with non‐hydroxy fatty acids and C18‐sphingosine and increased the level of esterified omega‐hydroxy fatty acid‐containing ceramides) and increased ceramide chain length in lesional as well as non‐lesional stratum corneum of AD patients. Partial changes for these parameters were already observed after 2 weeks, with a full response achieved after 8 weeks of dupilumab treatment. Conclusions Inhibition of IL‐4/IL‐13 signaling by dupilumab allows restoration of skin lipid composition and barrier function in patients with moderate‐to‐severe AD.
Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline
Authors: Navneet Singh, Sarah Temin, Sherman Baker, Elizabeth Blanchard, Julie R. Brahmer, Paul Celano, Narjust Duma, Peter M. Ellis, Ivy B. Elkins, Rami Y. Haddad, Paul J. Hesketh, Dharamvir Jain, David H. Johnson, Natasha B. Leighl, Hirva Mamdani, Gregory Masters, Pamela R. Moffitt, Tanyanika Phillips, Gregory J. Riely, Andrew G. Robinson, Rafael Rosell, Joan H. Schiller, Bryan J. Schneider, David R. Spigel, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2022)

To provide evidence-based recommendations updating the 2020 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer without driver alterations.ASCO updated recommendations on the basis of an ongoing systematic review of randomized clinical trials from 2018 to 2021.This guideline update reflects changes in evidence since the previous update. Five randomized clinical trials provide the evidence base. Outcomes of interest include efficacy and safety.In addition to 2020 options for patients with high programmed death ligand-1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%), nonsquamous cell carcinoma (non-SCC), and performance status (PS) 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression (TPS ≥ 50%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilumumab alone or nivolumab and ipilimumab plus chemotherapy. With negative (0%) and low positive PD-L1 expression (TPS 1%-49%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or nivolumab and ipilimumab plus chemotherapy. With high PD-L1 expression, SCC, and PS 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression, squamous cell carcinoma (SCC), and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With negative and low positive PD-L1 expression, SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With non-SCC who received an immune checkpoint inhibitor and chemotherapy as first-line therapy, clinicians may offer second-line paclitaxel plus bevacizumab. With non-SCC, who received chemotherapy with or without bevacizumab and immune checkpoint inhibitor therapy, clinicians should offer the options of third-line single-agent pemetrexed, docetaxel, or paclitaxel plus bevacizumab.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for <i>TP53</i>-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: Asmita Mishra, Roni Tamari, Amy E. DeZern, Michael T. Byrne, Mahasweta Gooptu, Yi-Bin Chen, H. Joachim Deeg, David Sallman, Phillip Gallacher, Anders Wennborg, Denice K. Hickman, Eyal C. Attar, Hugo F. Fernandez
Journal: Journal of Clinical Oncology (2022)

Outcomes are poor in TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), even after allogeneic hematopoietic stem-cell transplant (HCT). Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator.We conducted a phase II, multicenter, open-label trial to assess efficacy and safety of eprenetapopt combined with azacitidine as maintenance therapy after HCT (ClinicalTrials.gov identifier: NCT03931291). Patients with mTP53 MDS or AML received up to 12 cycles of eprenetapopt 3.7 g once daily intravenously on days 1-4 and azacitidine 36 mg/m2 once daily intravenously/subcutaneously on days 1-5 in 28-day cycles. The primary outcomes were relapse-free survival (RFS) and safety.Of the 84 patients screened for eligibility before HCT, 55 received a transplant. Thirty-three patients ultimately received maintenance treatment (14 AML and 19 MDS); the median age was 65 (range, 40-74) years. The median number of eprenetapopt cycles was 7 (range, 1-12). With a median follow-up of 14.5 months, the median RFS was 12.5 months (95% CI, 9.6 to not estimable) and the 1-year RFS probability was 59.9% (95% CI, 41 to 74). With a median follow-up of 17.0 months, the median overall survival (OS) was 20.6 months (95% CI, 14.2 to not estimable) and the 1-year OS probability was 78.8% (95% CI, 60.6 to 89.3). Thirty-day and 60-day mortalities from the first dose were 0% and 6% (n = 2), respectively. Acute and chronic (all grade) graft-versus-host disease adverse events were reported in 12% (n = 4) and 33% (n = 11) of patients, respectively.In patients with mTP53 AML and MDS, post-HCT maintenance therapy with eprenetapopt combined with azacitidine was well tolerated. RFS and OS outcomes were encouraging in this high-risk population.
Undiagnosed Diabetes in U.S. Adults: Prevalence and Trends
Authors: Michael Fang, Dan Wang, Josef Coresh, Elizabeth Selvin
Journal: Diabetes Care (2022)

OBJECTIVE Confirmatory testing is recommended for diabetes diagnosis in clinical practice. However, national estimates of undiagnosed diabetes are based on single elevated test measures, potentially resulting in overestimation. Our objective was to update trends in undiagnosed diabetes using definitions consistent with clinical practice. RESEARCH DESIGN AND METHODS We included 30,492 adults (aged ≥20 years) from the National Health and Nutrition Examination Survey (1988–2020). Among adults without diagnosed diabetes, confirmed undiagnosed diabetes was defined as having both elevated levels of fasting plasma glucose (FPG) (≥126 mg/dL) and elevated glycated hemoglobin (HbA1c; ≥6.5%), and persistent undiagnosed diabetes was defined as having elevated HbA1c or FPG levels, adjusted for the within-person variability in HbA1c and FPG tests. RESULTS From the periods 1988–1994 to 2017 to March 2020, there was an increase in the prevalence of diagnosed diabetes (from 4.6% to 11.7%), but no change in prevalence of persistent undiagnosed diabetes (from 2.23% to 2.53%) or confirmed undiagnosed diabetes (from 1.10% to 1.23%). Consequently, the proportion of all undiagnosed diabetes cases declined from 32.8% to 17.8% (persistent undiagnosed diabetes) and from 19.3% to 9.5% (confirmed undiagnosed diabetes). Undiagnosed diabetes was more prevalent in older and obese adults, racial/ethnic minorities, and those without health care access. Among persons with diabetes, Asian Americans and those without health care access had the highest proportion of undiagnosed cases, with rates ranging from 23% to 61%. CONCLUSIONS From 1988 to March 2020, the proportion of undiagnosed diabetes cases declined substantially, suggesting major improvements in diabetes screening and detection. Undiagnosed diabetes currently affects 1–2% of US adults; up to 90% of all cases are diagnosed.
Author Correction to: SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells
Authors: Daniel Perez-Zsolt, Jordana Muñoz-Basagoiti, Jordi Rodon, Marc Elosua-Bayes, Dàlia Raïch-Regué, Cristina Risco, Martin Sachse, Maria Pino, Sanjeev Gumber, Mirko Paiardini, Jakub Chojnacki, Itziar Erkizia, Xabier Muñiz-Trabudua, Ester Ballana, Eva Riveira-Muñoz, Marc Noguera-Julian, Roger Paredes, Benjamin Trinité, Ferran Tarrés-Freixas, Ignacio Blanco, Victor Guallar, Jorge Carrillo, Julià Blanco, Amalio Telenti, Holger Heyn, Joaquim Segalés, Bonaventura Clotet, Javier Martinez-Picado, Júlia Vergara-Alert, Nuria Izquierdo-Useros
Journal: Cellular and Molecular Immunology (2022)

In the version of this correspondence initially published, one of the SARS-CoV-2 variants used in Fig. 1B, which was originally described in the article as the SARS-CoV-2 variant 'B.1.1.248.2Gamma', is actually the 'P.2 Zeta' SARS-CoV-2 variant of interest.The GISAID accession ID EPI_ISL_1831696 provided is correct, but it belongs to the Zeta variant.The results and conclusions are not affected by this unintentional inaccuracy.0.
Glucose metabolism controls human γδ T-cell-mediated tumor immunosurveillance in diabetes
Authors: Xiaofeng Mu, Zheng Xiang, Yan Xu, Jing He, Jianwen Lu, Yuyuan Chen, Xiwei Wang, Chloe Ran Tu, Yanmei Zhang, Wenyue Zhang, Zhinan Yin, Wing-hang Leung, Yu-Lung Lau, Yinping Liu, Wenwei Tu
Journal: Cellular and Molecular Immunology (2022)
Ethnic minority staff felt “vulnerable” during pandemic, says senior leader
Authors: Elisabeth Mahase
Journal: BMJ (2022)

A young previously healthy patient presented with sepsis and cavitating pneumonia. <i>Campylobacter rectus</i> was isolated from blood cultures and subsequent CT neck showed an internal jugular vein thrombosis. Treatment was with antibiotics, anticoagulation and supportive management. Lemierre’s syndrome is an infectious thrombophlebitis of the internal jugular vein. Although a rare diagnosis since the use of penicillin for treatment of acute pharyngitis, it is being reported with increasing frequency. Usually associated with <i>Fusobacterium</i> spp, we believe that this is the first reported case of Lemierre’s caused by <i>C. rectus—</i>an anaerobic member of the human oral cavity flora, usually associated with localised periodontal disease. The bacillus was isolated from blood during the acute presentation.
Metabolic, Intestinal, and Cardiovascular Effects of Sotagliflozin Compared With Empagliflozin in Patients With Type 2 Diabetes: A Randomized, Double-Blind Study
Authors: Maximilian G. Posch, Niklas Walther, Ele Ferrannini, David R. Powell, Phillip Banks, Suman Wason, Raphael Dahmen
Journal: Diabetes Care (2022)

Inhibiting sodium-glucose cotransporters (SGLTs) improves glycemic and cardiovascular outcomes in patients with type 2 diabetes (T2D). We investigated the differential impact of selective SGLT2 inhibition and dual inhibition of SGLT1 and SGLT2 on multiple parameters.Using a double-blind, parallel-group design, we randomized 40 patients with T2D and hypertension to receive the dual SGLT1 and SGLT2 inhibitor sotagliflozin 400 mg or the selective SGLT2 inhibitor empagliflozin 25 mg, with preexisting antihypertensive treatment, for 8 weeks. In an in-house testing site, mixed-meal tolerance tests (MMTTs) and other laboratory and clinical evaluations were used to study metabolic, intestinal, cardiovascular, and urinary parameters over 24 h.Changes from baseline in glycemic and blood pressure control; intestinal, urine, and metabolic parameters; and cardiovascular biomarkers were generally similar with sotagliflozin and empagliflozin. During the breakfast MMTT, sotagliflozin significantly reduced incremental area under the curve (AUC) values for postprandial glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) and significantly increased incremental AUCs for postprandial glucagon-like peptide 1 (GLP-1) relative to empagliflozin, consistent with sotagliflozin-mediated inhibition of intestinal SGLT1. These changes waned during lunch and dinner MMTTs. Both treatments significantly lowered GIP incremental AUCs relative to baseline over the 14 h MMTT interval; the most vigorous effect was seen with sotagliflozin soon after start of the first meal of the day. No serious or severe adverse events were observed.Changes from baseline in glycemic and blood pressure control, cardiovascular biomarkers, and other parameters were comparable between sotagliflozin and empagliflozin. However, sotagliflozin but not empagliflozin inhibited intestinal SGLT1 after breakfast as shown by larger changes in postprandial glucose, insulin, GIP, and GLP-1 AUCs, particularly after breakfast. Additional study is warranted to assess the clinical relevance of transient SGLT1 inhibition and differences in incretin responses (NCT03462069).
Characterising smoking and smoking cessation attempts by risk of alcohol dependence: A representative, cross-sectional study of adults in England between 2014-2021
Authors: Claire Garnett, Melissa Oldham, Lion Shahab, Harry Tattan-Birch, Sharon Cox
Journal: The Lancet Regional Health - Europe (2022)

There is a strong shared association between smoking tobacco and drinking alcohol. This study aimed to compare smoking prevalence and smoking characteristics in drinkers who were versus were not at risk of alcohol dependence in England.
Subclinical Atherosclerosis in Young, Socioeconomically Vulnerable Hispanic and Non-Hispanic Black Adults
Authors: Josep Iglesies-Grau, Rodrigo Fernandez-Jimenez, Raquel Diaz-Munoz, Risa Jaslow, Amaya de Cos-Gandoy, Gloria Santos-Beneit, Christopher A. Hill, Alexandra Turco, Daniella Kadian-Dodov, Jason C. Kovacic, Zahi A. Fayad, Valentin Fuster
Journal: Journal of the American College of Cardiology (2022)
Contributions of the Women’s Health Initiative to Cardiovascular Research
Authors: Michael J. LaMonte, JoAnn E. Manson, Garnet L. Anderson, Laura D. Baker, Jennifer W. Bea, Charles B. Eaton, Shawna Follis, Kathleen M. Hayden, Charles Kooperberg, Andrea Z. LaCroix, Marian C. Limacher, Marian L. Neuhouser, Andrew Odegaard, Marco V. Perez, Ross L. Prentice, Alexander P. Reiner, Marcia L. Stefanick, Linda Van Horn, Gretchen L. Wells, Eric A. Whitsel, Jacques E. Rossouw
Journal: Journal of the American College of Cardiology (2022)
A precise and efficient adenine base editor
Authors: Tianxiang Tu, Zongming Song, Xiaoyu Liu, Shengxing Wang, Xiaoxue He, Haitao Xi, Jiahua Wang, Tong Yan, Haoran Chen, Zhenwu Zhang, Xiujuan Lv, Jineng Lv, Xiu-Feng Huang, Junzhao Zhao, Chao-Po Lin, Caixia Gao, Jinwei Zhang, Feng Gu
Journal: Molecular Therapy (2022)

Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in <i>Rhodopsin</i> for autosomal dominant retinitis pigmentosa. It reduces bystander editing by ∼4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.
Perceived Barriers to Serving on National Institutes of Health Scientific Review Groups Experienced by Black and African American Scientists
Authors: Eric K. Soule, Sabrina Ford, Robert L. Newton, Alisha Thomas, Thomas Eissenberg
Journal: JAMA Network Open (2022)

African American and Black scientists are awarded disproportionately fewer National Institutes of Health (NIH) grants than White scientists. Increasing Black representation on NIH scientific review groups (SRGs) likely will contribute to increased equity in funding rates because research topics of Black and African American scientists' submitted applications will be more highly valued; however, Black and African American scientists often perceive barriers that prevent them from serving on NIH SRGs.To examine perceived barriers that prevent Black and African American scientists from serving on NIH SRGs.This qualitative study used a mixed methods online approach with a convenience sample of Black and African American scientists to identify barriers to NIH grant review participation. Eligible participants were recruited online from professional organizations with primarily Black and African American membership. From February through April 2021, participants were asked to identify barriers to serving on NIH SRGs using concept mapping. Participants brainstormed statements describing barriers to serving on NIH SRGs, sorted statements into content themes, and rated statements on how true they were. Multidimensional scaling and a hierarchical cluster analysis identified content themes. Data analysis was conducted in May and June of 2021.Self-reported barriers to serving on an NIH SRG among Black and African American scientists.A total of 52 scientists participated in both phases of the study (mean [SD] age, 42.3 [8.2] years; 46 women [88.5%]). Participants provided 68 unique statements that were organized into 9 thematic clusters describing barriers to serving on NIH SRGs. Themes included structural racism, diversity not valued, toxic environment, review workload demand, lack of reward, negative affect about the review process, competing demands at home institution, lack of opportunity, and perceptions of being unqualified.Black and African American scientists reported many barriers to serving on NIH SRGs that are unique to Black and African American scientists, as well as barriers that transcend race but are exacerbated by structural racism. This study provides NIH with concrete opportunities to address realized barriers to increase inclusion of Black and African American scientists on NIH SRGs, fund more Black and African American scientists, and ultimately reduce health inequities in the US.
MicroRNA-21-5p promotes mucosal type 2 inflammation via regulating GLP1R/IL-33 signaling in chronic rhinosinusitis with nasal polyps
Authors: Ge Luan, Ming Wang, Jing Yuan, Xiangting Bu, Yang Wang, Sun Ying, Chengshuo Wang, Luo Zhang
Journal: Journal of Allergy and Clinical Immunology (2022)
Integrated metabolomics revealed the fibromyalgia-alleviation effect of Mo2C nanozyme through regulated homeostasis of oxidative stress and energy metabolism
Authors: Dingkun Zhang, Ling Jiang, Li Li, Xin Li, Wen Zheng, Luolan Gui, Yin Yang, Yueqiu Liu, Linghui Yang, Jing Wang, Yixiao Xiong, Liwei Ji, Yan Deng, Xin Liu, Qinqin He, Xinyi Hu, Xin Liu, Rong Fan, Yang Lu, Jingping Liu, Jingqiu Cheng, Hao Yang, Tao Li, Meng Gong
Journal: Biomaterials (2022)
Criteria for Defining Stages of Cardiogenic Shock Severity
Authors: Navin K. Kapur, Manreet Kanwar, Shashank S. Sinha, Katherine L. Thayer, A. Reshad Garan, Jaime Hernandez-Montfort, Yijing Zhang, Borui Li, Paulina Baca, Fatou Dieng, Neil M. Harwani, Jacob Abraham, Gavin Hickey, Sandeep Nathan, Detlef Wencker, Shelley Hall, Andrew Schwartzman, Wissam Khalife, Song Li, Claudius Mahr, Ju H. Kim, Esther Vorovich, Evan H. Whitehead, Vanessa Blumer, Daniel Burkhoff
Journal: Journal of the American College of Cardiology (2022)